Predicting Liver‐Related Outcomes in People With Nonalcoholic Fatty Liver Disease: The Prognostic Value of Noninvasive Fibrosis Tests

Abstract

It remains unclear whether screening for advanced fibrosis in the community can identify the subgroup of people with nonalcoholic fatty liver disease (NAFLD) at higher risk for development of liver‐related complications. We aimed to determine the prognostic value of baseline noninvasive fibrosis tests for predicting liver‐related outcomes and mortality in patients with NAFLD from type 2 diabetes (T2D) clinics or primary care. Patients (n = 243) who were screened for NAFLD with advanced fibrosis by using NAFLD fibrosis score (NFS), fibrosis 4 score (FIB‐4), enhanced liver fibrosis (ELF) test, and liver stiffness measurements (LSMs) were followed up for clinical outcomes by review of electronic medical records. During a median follow‐up of 50 months, decompensated liver disease or primary liver cancer occurred in 6 of 35 (17.1%) patients with baseline LSM > 13 kPa, 1 of 17 (5.9%) patients with LSM 9.5‐13 kPa, and in no patients with LSM < 9.5 kPa. No patient with low‐risk NFS developed liver decompensation or liver‐related mortality. Following repeat NFSs at the end of follow‐up, all patients with a liver‐related complication were in the high‐risk NFS category. Patients who developed liver‐related complications were also more likely to have baseline high‐risk FIB‐4 scores or ELF test ≥9.8 compared to patients who did not develop liver outcomes. Conclusion: Liver fibrosis risk stratification in non‐hepatology settings can identify the subset of patients at risk of liver‐related complications. Although the rate of development of a decompensation event or hepatocellular carcinoma was low (2.1% per year) in our patients with compensated cirrhosis (LSM > 13 kPa), these events are projected to lead to a substantial increase in NAFLD‐related disease burden over the next decade due to the high prevalence of NAFLD in people with obesity and T2D.

Letter: non‐invasive prediction models to exclude cirrhosis in NAFLD—not everyone fits the mould. Authors' reply

“…Whilst some studies have reported decreased accuracy of FIB-4 in patients with diabetes, 5 FIB-4 has been associated with an increased risk of liver-related morbidity and mortality in a cohort of patients with an even higher prevalence of diabetes than in our study. 6 In our derivation and validation cohorts, the mean BMI was 34-35 kg/m 2 , with most patients having BMI > 30 and ~15% with BMI >40, which is representative of the general NAFLD population. Our study was not powered to investigate the performance of our cutoffs in subgroups such as patients with diabetes or class III obesity.…”

A practical use of noninvasive tests in clinical practice to identify high‐risk patients with nonalcoholic steatohepatitis

“…A few other serum biomarkers measure different components of fibrosis 54,55,57–64 In clinical practice, ELF is the first serum biomarker for which the FDA has given a de novo marketing authorisation for assessment of prognosis in advanced fibrosis among patients with NASH. The ELF score which consists of serum levels for three matrix turnover proteins (hyaluronic acid, TIMP‐1 and PIIINP) has an AUROC of 0.90 with 80% sensitivity and 90% specificity for detecting advanced fibrosis.…”

“…The ELF score uses two distinct cut off values to determine risk of fibrosis. Specifically, ELF score <9.8 indicates low risk, ELF score ≥ 9.8 < 11.3 indicates mid risk and a score ≥11.3 indicates higher risk for advanced fibrosis 53,54,57–64 . Additionally, ELF is a prognostic test where a unit increase in ELF score is associated with a doubling of risk 60 .…”

“…52 However, given the various versions of the Fibrometer, further assessment of its performance among patients with NAFLD and its role in care pathways of patients with NAFLD is recommended. 52 A few other serum biomarkers measure different components of fibrosis 54,55,[57][58][59][60][61][62][63][64] In clinical practice, ELF is the first serum biomarker indicates higher risk for advanced fibrosis. 53,54,[57][58][59][60][61][62][63][64] Additionally, ELF is a prognostic test where a unit increase in ELF score is associated with a doubling of risk.…”

“…52 A few other serum biomarkers measure different components of fibrosis 54,55,[57][58][59][60][61][62][63][64] In clinical practice, ELF is the first serum biomarker indicates higher risk for advanced fibrosis. 53,54,[57][58][59][60][61][62][63][64] Additionally, ELF is a prognostic test where a unit increase in ELF score is associated with a doubling of risk. 60 In this context, ELF's high sensitivity and specificity are more apparent in settings with high prevalence of advanced fibrosis (>50%).…”